Evidence map›Paper›PMID 41430032›Full record

ArticleSignal transduction and targeted therapy2025

Scarless circular mRNA-based CAR-T cell therapy elicits superior antitumor efficacy.

Qinchao Hu, Hui Zhao, Kaicheng Zhou, Xuefei Tian, Qian Wang, Xianxin Hua, Xuyao Zhang

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed.

  1. Article
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  6. Acta pharmaceutica Sinica. B · 2026
    Review
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  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Delivery platforms forFrontiers in immunology · 2026
    Review
  14. Frontiers in immunology · 2026
    Review
  15. Review
  16. Article
  17. Review
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  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Qinchao HuDepartment of Biological Medicines, School of Pharmaceutical Sciences & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China.
Hui ZhaoByterna Therapeutics, Shanghai, China. zhaohui@byterna.com.
Kaicheng ZhouDepartment of Biological Medicines, School of Pharmaceutical Sciences & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China.
Xuefei TianDepartment of Biological Medicines, School of Pharmaceutical Sciences & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China.
Qian WangDepartment of Biological Medicines, School of Pharmaceutical Sciences & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China.
Xianxin HuaDepartment of Cancer Biology, Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. huax@pennmedicine.upenn.edu.
Xuyao ZhangDepartment of Biological Medicines, School of Pharmaceutical Sciences & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University, Shanghai, China. xuyaozhang@fudan.edu.cn.ORCID 0000-0003-1654-5550

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32200745
6 · The paper itself

Abstract

Messenger RNA (mRNA)-based transient expression of chimeric antigen receptors (CARs) results in optimal safety profiles and provides promising opportunities to address existing challenges associated with viral vector-based CAR-T-cell therapies and to meet emerging medical needs for noncancerous indications. Conventional linear mRNAs, however, are intrinsically unstable and typically support short-lived protein expression, which can constrain therapeutic activity. Here, we engineered a high-efficiency permuted intron exon (PIE) platform to synthesize scarless circular mRNAs (cmRNAs) that drive robust CAR expression with extended durability. The scarless design avoids extraneous junction sequences, streamlining manufacturability and potentially reducing innate immune sensing. Compared with linear mRNAs, cmRNAs significantly increased both the magnitude and duration of anti-CD19 CAR and anti-GPRC5D CAR expression in primary human T cells. Functionally, cmRNA-based CAR-T cells elicited superior antitumor efficacy over their linear mRNA counterparts, as demonstrated by parallel lines of evidence, including in vitro antigen-specific cytotoxicity, cytokine release, and transcriptomics patterns consistent with sustained activation and absence of exhaustion signatures, as well as in vivo models demonstrating tumor elimination and prolonged survival benefits. Collectively, these findings position cmRNA as a next-generation mRNA modality for potent and controllable CAR expression, thereby providing a robust platform to unleash the full potential of mRNA technologies in cellular immunotherapy and precision medicine.

Indexed as

Immunotherapy, AdoptiveNeoplasmsReceptors, Chimeric AntigenRNA, CircularT-LymphocytesAnimalsCell Line, TumorHumansMiceReceptors, Chimeric AntigenRNA, Circular

Identifiers

PMID41430032
PMCPMC12722250

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.